Histone synthesis in the sea urchin is characterized by tissue and stage-specific expression of sequence variants for at least 3 of the 5 major histone. We are interested in isolating from the multiple copies of histone genes in the sea urchin genome those sequences which encode specific variants. Our approach entails operationally subdividing the total DNA sequence complement into 3 tentative categories to potentially enrich the variant sequences. These categories correspond to: a) sequences located internally in the major cluster (s). b) sequences at the ends of the major histone DNA cluster (s). c) sequences located outside the major cluster (s). We will use specific restriction endonucleases and recombinant DNA vectors to achieve this fractionation. Methods are proposed for screening the three categories of clones to identify those which specify variant proteins. The isolation of these DNA sequences will permit comparison of gene sets having homologous function but differential temporal expression during development. This should be useful in: a) Correlating DNA sequence organization with developmentally-regulated patterns of expression, b) understanding the evolution of repetitive genes, c) providing tools for the eventual identification of macromolecules that interact with DNA in vivo to regulate its function.